Lipopolysaccharide animal models of Parkinson’s disease: Recent progress and relevance to clinical disease

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerative movement disorders which is characterised neuropathologically by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (made predominately of α-synuclein) in the surviving neurons. Animal models of PD have improved our understanding of the disease and have played a critical role in the development of neuroprotective agents. Neuroinflammation has been strongly implicated in the pathogenesis of PD, and recent studies have used lipopolysaccharide (LPS), a component of gram-negative bacteria and a potent activator of microglia cells, to mimic the inflammatory events in clinical PD. Modulating the inflammatory response could ameliorate PD associated complications and thus, it is essential to understand the extent to which LPS models reflect human PD. This review will outline the routes of administration of LPS such as stereotaxic, systemic and intranasal, their ability to recapitulate neuropathological markers of PD, and mechanisms of LPS induced toxicity. We will also discuss the ability of the models to replicate motor symptoms and non-motor symptoms of PD such as gastrointestinal dysfunction, olfactory dysfunction, anxiety, depression and cognitive dysfunction.

Highlights

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  This review describes stereotaxic, intraperitoneal and intranasal LPS animal models of PD.

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  The ability of the models to replicate motor symptoms and non-motor symptoms of PD are analysed.

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  The possible mechanisms of LPS induced toxicity and their relevance to clinical PD are discussed.

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  Currently most evidence exists for the stereotaxic LPS model of PD.

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  Further characterisation of LPS models of PD is warranted.